Formocresol, the standard drug for pulpotomy therapy in children, has been criticized in recent years for cytotoxicity and potential for mutagenicity, carcinogenicity and systemic pathology. The bifunctional reagent, glutaraldehyde, shows promise as an alternative pulp agent by virtue of rapid and stable cross-linking with proteins, low antigenicity of its reaction products, reduced diffusion from a pulpotomy site, and expectations for minimal local and systemic toxicity. Before glutaraldehyde is recommended to the dental profession, we are proposing an evaluation of its efficacy and safety, with the objective of establishing optimal parameters for clinical trials. Our first objective will be to determine an optimal compromise between concentration and length of treatment as a guideline for further studies on systemic pathology and possible clinical trials of glutaraldehyde. First, the best combinations of strength of solution and duration of exposure will be determined in vitro. The assay chosen will measure the cross-linking of bovine serum albumin within a collagen gel following incubation in glutaraldehyde solutions, with time and concentration as variables. Optimal conditions suggested by this procedure will then be evaluated for biological effectiveness. An in vitro analysis will measure the residual enzyme activity in treated bovine pulp following treatment with glutaraldehyde. A follow-up study will examine the status of the radicular tissue of glutaraldehyde-treated rat molars using histochemical criteria. The extent of the in vivo inhibition of enzyme activity will then be correlated to the depth of penetration of glutaraldehyde in the pulp canal by autoradiography using 14C-glutaraldehyde. An additional test of in vivo fixation will involve the measurement of 131-1 which diffuses systemically from a pulp chamber after the canals have been treated with glutaraldehyde. After having established an optimal combination of concentration and duration of treatment for the use of glutaraldehyde, our next objective will be to quantify the systemic distribution of 14C-glutaraldehyde from pulpotomized teeth of rats. After determining the body load which escapes from the pulpotomy site, a systematic evaluation of potential somatic pathology will be undertaken. A comparable dose (and increments of that dose) will be infused into rats; at sacrifice, blood will be drawn for biochemical analyses and samples of major organs harvested for histologic studies.